In vitro and in vivo validation of the antiviral effect of hCypA against SARS-CoV-2 via binding to the RBD of spike protein

Woo-Ri Shin; Do-Young Kim; Sang Yong Kim; Gna Ahn; Dae-Young Park; Jiho Min; Ji-Young Ahn; Yang-Hoon Kim

doi:10.1016/j.ymthe.2024.03.029

In vitro and in vivo validation of the antiviral effect of hCypA against SARS-CoV-2 via binding to the RBD of spike protein

Mol Ther. 2024 Mar 25:S1525-0016(24)00170-9. doi: 10.1016/j.ymthe.2024.03.029. Online ahead of print.

Authors

Woo-Ri Shin¹, Do-Young Kim², Sang Yong Kim³, Gna Ahn⁴, Dae-Young Park², Jiho Min⁵, Ji-Young Ahn⁶, Yang-Hoon Kim⁷

Affiliations

¹ Department of Microbiology, Chungbuk National University, 1 Chungdae-Ro, Seowon-Gu, Cheongju 28644, South Korea; Department of Bioengineering, University of Pennsylvania, 210 S 33rd Street, Philadelphia, PA 19104, USA.
² Department of Microbiology, Chungbuk National University, 1 Chungdae-Ro, Seowon-Gu, Cheongju 28644, South Korea.
³ Department of Food Science and Biotechnology, Shin Ansan University, Danwon-Gu, Ansan 15435, Republic of Korea.
⁴ Department of Microbiology, Chungbuk National University, 1 Chungdae-Ro, Seowon-Gu, Cheongju 28644, South Korea; Center for Ecology and Environmental Toxicology, Chungbuk National University, Cheongju 28644, Republic of Korea.
⁵ Graduate School of Semiconductor and Chemical Engineering, Jeonbuk National University, 567 Baekje-daero, Deokjin-Gu Jeonju, Jeonbuk 54896, South Korea. Electronic address: jihomin@jbnu.ac.kr.
⁶ Department of Microbiology, Chungbuk National University, 1 Chungdae-Ro, Seowon-Gu, Cheongju 28644, South Korea. Electronic address: jyahn@chungbuk.ac.kr.
⁷ Department of Microbiology, Chungbuk National University, 1 Chungdae-Ro, Seowon-Gu, Cheongju 28644, South Korea. Electronic address: kyh@chungbuk.ac.kr.

PMID: 38532628
DOI: 10.1016/j.ymthe.2024.03.029

Abstract

The novel coronavirus disease 2019 has stimulated the rapid development of new biological therapeutics to inhibit SARS-CoV-2 infection; however, this remains a challenging task. In a previous study using structural analysis, we revealed that human cyclophilin A inhibits the entry of SARS-CoV-2 into host cells by interfering with the interaction of the receptor-binding domain of the spike protein with angiotensin-converting enzyme 2 on the host cell surface, highlighting its potential for antiviral therapy. For a comprehensive experimental validation, in this study, we verified the antiviral effects of human cyclophilin A against SARS-CoV-2, including its variants, using in vitro assays and experiments on an in vivo mouse model. Human cyclophilin A demonstrated a highly effective antiviral effect, with an 85% survival rate upon SARS-CoV-2 infection. It also reduced viral titers, inflammation in the lungs and brain, and cytokine release in the serum, suggesting a controlled immune response and potentially faster recovery. Overall, our study provides insights into the potential of human cyclophilin A as a therapeutic agent against SARS-CoV-2, which should guide future clinical trials that might provide an additional therapeutic option for patients.

Keywords: COVID-19; SARS-CoV-2; antiviral; cyclophilin A; cytokine storm; inflammation; spike protein; therapeutic.